Abstract: This invention characterizes the specific peptide fragment derived from specially prepared zinc charged fetuin and a method of preparation thereof, wherein the fragment was found to contain an apoptosis-inducing activity. Specifically, the amino acid sequence of this peptide is His Thr Phe Ser Gly Val Ala Ser Val Glu (SEQ ID NO: 1). The peptide induced apoptosis in LNCaP (prostate cancer) and HT-29 (colon cancer) cells without affecting CCD 18 Co (normal colon) cells. The in vitro tissue culture study demonstrated that the peptide is more potent than the parent molecule (full-length zinc charged fetuin) in inducing apoptosis. The peptide has a LD50 of 0.3-0.4 ?M, while the LD50 for zinc-charged fetuin is 3-10 ?M.

Abstract: Novel conjugates that are capable of inhibiting GSK-3 activity, a process of producing same, pharmaceutical compositions including same and methods of using same in the treatment of GSK-3 mediated conditions are disclosed. Methods of treating affective disorders using GSK-3 inhibitors are further disclosed.

Abstract: The present invention relates to novel chimeric C3-like Rho antagonists and their use for promoting repair and neuron survival in injured mammalian central and peripheral nervous system and for treating or preventing cancer.

Abstract: An process for the reversible modification of an amine-containing compound is described. Modification of the compound can be used to facilitate delivery of molecules to cells in vitro and in vivo or to alter interactions or activities the compounds. The described modifiers can also be utilized as cross-linkers.

Abstract: This invention relates to modified Vasoactive Intestinal Peptide (VIP)/Pituitary Adenylate Cyclase Activating Peptide (PACAP) Receptor 2 (VPAC2) agonists (VPAC2 agonists) comprising a VPAC2 agonist linked to a polyethylene glycol polymer, as well as related formulations, dosages, and methods of administration thereof for therapeutic purposes. These VPAC2 agonists, compositions, and methods are useful in providing a treatment option for those individuals afflicted with a metabolic disorder such as diabetes, impaired glucose tolerance, metabolic syndrome, or prediabetic states, by inducing glucose-dependent insulin secretion in the absence of the therapeutically limiting side effect of reducing or lowering blood pressure.

Abstract: The present application provides a method for predicting the functional site of a protein using data of the entire proteins of an organism of which genome data or cDNA data is known. More specifically, the present application provides a method for predicting a protein functional site, comprising the steps of calculating the frequency of occurrence of an oligopeptide in the entire proteins, calculating the value of each amino-acid residue contributing to the frequency of occurrence as the representative value of the function, and predicting the protein functional site by using the representative value of function as an indicator. The present also provides a system for predicting a functional site for automatically performing said methods.

Abstract: A molecular probe comprises two arsenic atoms and at least one cyanine based moiety. A method of producing a molecular probe includes providing a molecule having a first formula, treating the molecule with HgOAc, and subsequently transmetallizing with AsCl3. The As is liganded to ethanedithiol to produce a probe having a second formula. A method of labeling a peptide includes providing a peptide comprising a tag sequence and contacting the peptide with a biarsenical molecular probe. A complex is formed comprising the tag sequence and the molecular probe. A method of studying a peptide includes providing a mixture containing a peptide comprising a peptide tag sequence, adding a biarsenical probe to the mixture, and monitoring the fluorescence of the mixture.

Abstract: The present application discloses compositions and methods of synthesis and use of F-18 labeled molecules of use, for example, in PET imaging techniques. In particular embodiments, the labeled molecules may be peptides or proteins, although other types of molecules including but not limited to aptamers, oligonucleotides and nucleic acids may be labeled and utilized for such imaging studies. In preferred embodiments, the F-18 label may be conjugated to a targeting molecule by formation of a metal complex and binding of the F-18-metal complex to a chelating moiety, such as DOTA, NOTA, DTPA, TETA or NETA. In other embodiments, the metal may first be conjugated to the chelating group and subsequently the F-18 bound to the metal. In other preferred embodiments, the F-18 labeled moiety may comprise a targetable conjugate that may be used in combination with a bispecific or multispecific antibody to target the F-18 to an antigen expressed on a cell or tissue associated with a disease, medical condition, or pathogen.

Abstract: Novel conjugates of bacterial outer membrane binding peptides, preferably having bacterial sensitization activity, and immune cells chemotactic peptides, and pharmaceutical compositions containing same useful in the treatment of bacteremia and/or septicemia following infection by gram negative bacteria administered alone or in combination with conventional antibiotics.

Abstract: New and improved compounds for use in radiodiagnostic imaging or radiotherapy having the formula M-N—O—P-G, wherein M is the metal chelator (in the form complexed with a metal radionuclide or not), N—O—P is the linker, and G is the GRP receptor targeting peptide. Methods for imaging a patient and/or providing radiotherapy to a patient using the compounds of the invention are also provided. A method for preparing a diagnostic imaging agent from the compound is further provided. A method for preparing a radiotherapeutic agent is further provided.

Abstract: Fumaric acid amides of the general formula (I) wherein R1 represents OR3 or a D- or L-amino acid radical —NH—CHR4—COOH bonded via an amide bond, wherein R3 is hydrogen, a straight-chained or branched, optionally substituted C1-24 alkyl radical, a phenyl radical or C6-10 aralkyl radical and R4 is a side chain of a natural or synthetic amino acid and R2 represents a D- or L-amino acid radical —NH—CHR5—COOH bonded via an amide bond or a peptide radical comprising 2 to 100 amino acids bonded via an amide bond, wherein R5 is a side chain of a natural or synthetic amino acid, are used for preparing a drug (1) for the therapy of an autoimmune disease; (2) for use in transplantation medicine; (3) for the therapy of mitochondrial diseases; or (4) for the therapy of NF-kappaB mediated diseases.

Abstract: A process for forming a conjugate of a polyoxyalkylene polymer, such as polyethylene glycol, with a compound containing an amine group(s) and/or a sulfide group(s) by reacting the compound with an acrylate terminated polyoxyalkylene, such as polyethylene glycol terminated at one end with acrylate or methacrylate and terminated at the other end with a methoxy group. The reaction is believed to be a Michael addition. When the compound contains primary amine groups, such as the surface primary amine groups of a PAMAM dendrimer, it is usually desirable to convert the primary amine groups to secondary amine groups before the reaction with the acrylate terminated polyoxyalkylene.

Abstract: A novel compound, 2?/3?-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2? and 3? regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2?-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2?/3?-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2?/3?-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2?/3?-O-acetyl-ADP-ribose are also provided.

Abstract: The present invention provides compounds which are useful as multifunctional labels in proteomics studies. The labels of the present invention are both lysine specific and increase the overall sequence coverage obtained in polypeptide mapping experiments, by for example, increasing the ionization efficiencies of lysine-terminated tryptic fragments. In certain aspects, the labels of the present invention can be used to measure differential quantitation, as for example, deuterium(s) can easily be introduced during their synthesis. In one aspect, a C-terminal derivatized lysine biases the fragment ion intensities strongly toward C-terminal fragment ions, resulting in a highly simplified tandem mass spectrum. In further aspects, the number of lysine residues can be determined in a polypeptide.

Abstract: Disclosed herein are compounds that may be characterized by some as cyanine and indocyanine dye bioconjugates. Compounds disclosed herein may be utilized (e.g., in the form of a pharmaceutically acceptable composition) in a number of medical procedures, such as in the visualization and detection of tumors.

Abstract: The prodrug of the invention is a modified form of a therapeutic agent and comprises a therapeutic agent, an oligopeptide, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by the enzyme Thimet oligopeptidase, or TOP. Also disclosed are methods of designing prodrugs by utilizing TOP-cleavable sequences within the conjugate and methods of treating patients with prodrugs of the invention.

Abstract: The invention is directed to peptide modulators of Pin1 and Pin1-related proteins and the use of such modulators for treatment of Pin1 associated states, e.g., for the treatment of cancer or neurodegenerative disease.

Abstract: The present invention discloses methods and materials for delivering a cargo compound into a brain cancer cell and/or across the blood-brain barrier. Delivery of the cargo compound is accomplished by the use of protein transport peptides derived from Neisseria outer membrane proteins, such as Laz. The invention also provides synthetic transit peptides comprised of the pentapeptide AAEAP. The invention further discloses methods for treating cancer, and specifically brain cancer, as well as other brain-related conditions. Further, the invention provides methods of imaging and diagnosing cancer, particular brain cancer.

Abstract: This invention relates to a process for purifying a polypeptide, a capture tag useful for purifying a polypeptide and a periodate-cleavable amino acid derivative useful for purifying a polypeptide. The polypeptide to be purified comprises a vicinal-amino-thiol, vicinal-amino-hydoxyl, vicinal-diol or vicinal-diamino group. The purification process comprises attaching the polypeptide to a purification matrix by contacting the polypeptide with a purification matrix comprising aldehyde or ketone groups under conditions which favor formation of a heterocyclic ring system, washing the purification matrix, and releasing the polypeptide from the purification matrix.

Abstract: The present invention provides novel fluorophore compounds.

Abstract: The present invention relates to a method for preparing conjugates of an active substance and hydroxyalkyl starch and to conjugates of an active substance and hydroxyalkyl starch, preferably hydroxyethyl starch, wherein the conjugates are prepared by covalently linking the hydroxyalkyl starch and the active substance by a chemical residue having a structure according to formula (I) or formula (I?) or formula (I?) wherein R1, R2, R2?, R3, R3? and R4 are independently selected from the group consisting of hydrogen, an optionally suitably substituted, linear, cyclic and/or branched alkyl, aryl, heteroaryl, aralkyl, and heteroaralkyl group, preferably hydrogen.

Abstract: The invention relates to the field of compositions comprising a protein, more specifically to pharmaceutical compositions. More specifically, the invention relates to the detection and/or removal of conformationally altered proteins and/or molecules comprising a cross-? structure from a pharmaceutical composition or any of its constituents comprising a protein. The present invention discloses that unwanted and/or toxic side effects of pharmaceuticals are caused by proteins present in said pharmaceutical and adopting a cross-b structure conformation.

Abstract: The invention relates a method for preparing modified proteins having an increased capacity to bind divalent cations. For example the concentration of calcium at which Ca2+ induced aggregation occurs is increased by subjecting a protein to Maillard reaction conditions. Such modified proteins are of use for making calcium fortified food products.

Abstract: The present invention provides methods for labeling One or two oxygen atom(s) in a carboxyl group of a carboxyl-containing compound with an oxygen isotope selected from oxygen-17 (17O) or oxygen-18 (18O). The methods of the present invention are characterized in that an activated ester of the carboxyl-containing compound (carboxylic acid) is reacted with H217O or H218O in the presence of an activator. In the methods of the present invention, the reaction between the activated ester of a carboxylic acid and H217O or H218O can be allowed to proceed without including drastic conditions such as strongly acidic conditions or alkaline hydrolysis because an activator is used.

Abstract: The invention provides compositions and methods of identifying, modifying and producing modified target molecules, including therapeutic molecules by modification with non-natural amino acids. Certain aspects of the invention include methods of adding a chemical moiety to a target molecule, and the compositions resulting therefrom. Certain aspects of the invention also relate to kits for identifying, modifying and producing modified target molecules described herein.

Abstract: A novel for amidation of C-terminal carboxyl groups of peptides is devised, which methods avoids undesired epimerisation of the ?-carbon of the C-terminal amino acid yielding diastereoisomeric variants of the amidated peptide.

Abstract: The present invention encompasses peptides that selectively activate the VPAC2 receptor and are useful in the treatment of diabetes.

Abstract: The invention features compositions and methods for site-specific modification of proteins by incorporation of an aldehyde tag. Enzymatic modification at a sulfatase motif of the aldehyde tag through action of a formylglycine generating enzyme (FGE) generates a formylglycine (FGly) residue. The aldehyde moiety of FGly residue can be exploited as a chemical handle for site-specific attachment of a moiety of interest to a polypeptide.

Abstract: Molecules having potential biological activity, particularly peptoids, that are conjugated to solid phase supports, spacer groups, and/or ligation moieties, and methods of their preparation, are described. In some instances, the molecules of the invention are made entirely by solid phase synthesis. In other instances, the spacer groups are hydrophilic and compositions containing them, and to solid phase synthesis of varied structure peptoids using chemoselective ligation moieties.

Abstract: The present invention is directed to a somatostatin antagonist according to formula (I): A1-cyclo {D-Cys-A2-D-Trp-A3-A4-Cys}-A5Y1, wherein A1 is an optionally substituted aromatic a-amino acid; A2 is an optionally substituted aromatic ?-amino acid; A3 is Dab, Dap, Lys or Om; A4 is ?-Hydroxyvaline, Ser, Hser, or Thr; A5 is an optionally substituted D- or L-aromatic amino acid; and Y1 is OH, NH2 or NHR1? where RI is (C1-6)alkyl; wherein each said optionally substituted aromatic amino acid is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, NO2, OH, CN, (C1-6) alkyl, (C2-6) alkenyl, (C2-6) alkynyl, (C1-6)alkoxy, Bzl, O-Bzl, and NR9R10? wherein R9 ad R10 each is independently H, O, or (C1-6) alkyl; and wherein the amine nitrogen of each of amide peptide bond and the amino group of A1 of formula (I) is optionally substituted with a methyl group, provided that there is at least one said methyl group; or a pharmaceutically acceptable salt thereof,

Abstract: Methods for forming peptide derivatives using functional moieties and peptide derivatives are provided. Further, methods for using peptide derivatives to form silicon-based composite materials and silicon-based composite materials formed thereby are provided. The silicon-based composite materials may have features on the nanoscale, and the materials may exhibit characteristics derived from the functional moieties on the peptide derivatives. It is emphasized that this abstract is provided to comply with the rules requiring an abstract which will allow a searcher or other reader to quickly ascertain the subject matter of the technical disclosure. It is submitted with the understanding that is will not be used to interpret or limit the scope or meaning of the claims. 37 CFR 1.72(b).

Abstract: The invention provides immunomodulatory compounds and methods for immunomodulation of individuals using the immunomodulatory compounds.

Abstract: Disclosed herein are non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of possible functionalities, but typical have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid polypeptides that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such polypeptides. Typically, the modified non-natural amino acid polypeptides include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid polypeptides and modified non-natural amino acid polypeptides, including therapeutic, diagnostic, and other biotechnology uses.

Abstract: Peptide amphiphile compounds, compositions and methods for self-assembly or nanofibrous network formation under neutral or physiological conditions.

Abstract: The product of the invention is a modified form of a therapeutic agent and comprises a therapeutic agent, an oligopeptide having a plasmin peptide substrate of 2-4 amino acids and mono- or di-peptide linkage, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by plasmin. Also disclosed are methods of making and using the prodrug compounds.

Abstract: A compound is provided that has the formula NH2CH2CH2CHR1C(O)N—R ??(I) where R1 is p-chlorophenyl, R is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine blood brain barrier (BBB) peptide, membrane translocating protein, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptide transferrin, glucosylamine, amino saccharin, lactylamine, leucine, tryptophan, glutamate and amino cholines.

Abstract: The invention provides new processes for preparing polyglutamic acid-therapeutic agent conjugates for clinical development and pharmaceutical use, and polyglutamic acid-therapeutic agent conjugates prepared by these processes.

Abstract: Methods for preparing viral neuraminidase inhibitors including antiviral peptides by specifically chemically modifying disulfide bonds in precursor molecules. A method of inhibiting viral neuraminidases by administering a viral neuraminidase inhibitor comprising an antiviral peptide prepared by the above methods and inhibiting the viral neuraminidase. Therapeutics for inhibiting viral neuraminidases, including effective amounts of viral neuraminidase inhibitors including antiviral peptides derived from selectively chemically modified disuifide bonds in precursor molecules, and present in a pharmaceutically acceptable carriers.

Abstract: Provided herein are methods for introducing fluorine atom onto a biomolecule comprising: (i) providing a linker comprising a thiol-reactive terminus and an azido/alkyne-reactive terminus; (ii) reacting the thiol-reactive terminus of the linker with a biomolecule comprising at least one thiol group or a reactive derivative thereof; and (iii) subsequently reacting the azido/alkyne-reactive terminus of the linker with a fluorine-substituted azide or alkyne respectively. Also provided are compositions and method of synthesis of bifunctional linkers and bioconjugates as well as radio-diagnostic agents comprising fluorine-labeled biomolecules.

Abstract: The invention concerns a method for binding, in solution, at least a peptide composition and at least a lipophilic vector bearing an aldehyde function, the coupling comprising a step which consists in producing a hydrazone bond between the peptide compound and the lipophilic vector. The invention also concerns lipophilic vectors for use in this method, lipopeptides obtained by this method, uses of the lipopeptides for cell screening, and the applications of the invention, in particular for preparing targeting of an active principle of the peptide kind (for example hormone or neuropeptide) through physiological barriers such as cell membranes.

Abstract: The present invention concerns multimeric proteinaceous molecules comprising at least two members that bind each other via a region of noncovalent interaction, wherein a first of said members comprises a conditionally reactive group that, when activated, cleaves a covalent bond within said first member. Cleavage of the covalent bond results in a reduction in the binding strength with which the at least two members bind to each other via said region of noncovalent interaction. The reduction in the binding strength can result in the separation of the members under mild conditions.

Abstract: Identified herein is the location of the MN protein binding site, and MN proteins/polypeptides that compete for attachment to vertebrate cells with immobilized MN protein. Such MN proteins/polypeptides prevent cell-cell adhesion and the formation of intercellular contacts. The MN protein binding site is a therapeutic target that can be blocked by organic or inorganic molecules, preferably organic molecules, more preferably proteins/polypeptides that specifically bind to that site. Therapeutic methods for inhibiting the growth of preneoplastic/neoplastic vertebrate cells that abnormally express MN protein are disclosed. Vectors are provided that encode the variable domains of MN-specific antibodies and a flexible linker polypeptide separating those domains. Further vectors are disclosed that encode a cytotoxic protein/polypeptide operatively linked to the MN gene promoter, and which vectors preferably further encode a cytokine.

Abstract: Conjugates of porphyrin, chlorophyll and bacteriochlorophyll photosensitizers with RGD-containing peptides or RGD peptidomimetics are provided that are useful for photodynamic therapy (PDT), particularly vascular-targeted PDT (VTP), of tumors and normeoplastic vascular diseases such as age-related macular degeneration, and for diagnosis of tumors by different techniques.

Abstract: Methods for introducing fluorine atom onto a polypeptide are provided. Also provided are linkers, bioconjugates, and bifunctional compound agents made using the methods, linkers, and bioconjugates. The methods comprise: (i) providing a linker comprising a thiol-reactive terminus and an aldehyde-reactive terminus; (ii) reacting the thiol-reactive terminus of the linker with a polypeptide comprising at least one thiol group or a reactive derivative thereof; and (iii) subsequently reacting the aldehyde-reactive terminus of the linker with a fluorine-substituted aldehyde.

Abstract: Disclosed herein are methods for regulation of fat and/or cholesterol uptake from the gastrointestinal tract and/or regulation of plasma fat and/or cholesterol levels comprising administering to a mammal in need thereof an effective amount of a regulator of pancreatic IB PLA2 functionality. Also disclosed herein are methods of regulating the function of a polypeptide of interest comprising inserting of the 62-66 loop region of a pancreatic IB PLA2 amino acid sequence into the polypeptide of interest; and administering an effective amount of a regulatory molecule that effects its regulation through said amino acid sequence. Further disclosed are novel bile salt compounds that regulate pancreatic IB PLA2. Methods for detecting altered pancreatic IB PLA2 function and methods for identifying an agent suitable for regulating pancreatic IB PLA2 enzyme functionality are also disclosed.

Abstract: The present invention relates to PGA-vitamin complex containing poly-?-glutamic acid(PGA), vitamin preparations containing said PGA-vitamin complex or cosmetic compositions. The inventive PGA-vitamin complex having excellent hygroscopicity, moisturizing property and skin compatibility, which is a complex of poly-?-glutamic acid and vitamin, has the effect of sustained-release as well as improves stability of vitamin having the functions, such as promotion of metabolism, anti-oxidation effect, protection of cell wall, increasing immunity, prevention of dry skin and keratinization, anti-wrinkles and moisturizing skin, thereby being useful as cosmetic compositions and sustained-release vitamin preparations for various applications.

Abstract: The present invention provides a branched polyalkylene glycol wherein three or more single-chain polyalkylene glycols and a group having reactivity with an amino acid side chain, the N-terminal amino group or the C-terminal carboxyl group in a polypeptide or a group convertible into the group having reactivity are bound; and a physiologically active polypeptide modified with the branched polyalkylene glycol.

Abstract: An angiotensin derivative comprising at least one angiotensin peptide moiety coupled to a peptide carrier-binding moiety which can be used for therapy and prophylaxis of conditions associated with the renin activated angiotensin system.

Abstract: In the present specification is disclosed a melanocyte-stimulating hormone inhibitory composition which comprises, as the active ingredient, a di- or tripeptide derivative having a certain naphthyl group or the salts thereof, or a melanocyte-stimulating hormone inhibitory compound having a 50% inhibitory concentration of cAMP production (IC50) of 100 nM or less, which composition can prevent pigmentation, or can prevent, improve or recover from immune abnormality or immunodeficiency, or regulate body weight by appetite control, and also can be used as cosmetics or external preparations for the skin, and in addition, can be produced easily, and are excellent in the stability during storage.

Abstract: A method is provided for introducing a GAG binding site into a protein comprising the steps: identifying a region in a protein which is not essential for structure maintenance introducing at least one basic amino acid into said site and/or deleting at least one bulky and/or acidic amino acid in said site, whereby said GAG binding site has a GAG binding affinity of Kd?10 ?M, preferably ?1 ?M, still preferred ?0.1 ?M, as well as modified GAG binding proteins.